Splenic function and IgM-memory B cells in Crohn's disease patients treated with infliximab

Antonio Di Sabatino, M Manuela Rosado, Paolo Cazzola, Paolo Biancheri, Francesco Paolo Tinozzi, Maria Rita Laera, Laura Cantoro, Alessandro Vanoli, Rita Carsetti, Gino Roberto Corazza

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19 Citations (Scopus)

Abstract

BACKGROUND: Under experimental chronic inflammation, tumor necrosis factor (TNF)-alpha plays a role in damaging spleen marginal zone. This latter has a crucial function in mounting B cell-dependent immune responses against infections by encapsulated bacteria. In Crohn's disease (CD), a chronic inflammatory disorder where TNF-alpha is centrally involved, impaired splenic function may increase the susceptibility to bacterial infections. On this basis, we aimed to investigate the influence of anti-TNF therapy on splenic function in CD patients.

METHODS: Peripheral blood samples were obtained from 15 CD patients before and after treatment with infliximab administered at weeks 0, 2, and 6 at a dose of 5 mg/kg. Counting of erythrocytes with membrane abnormalities (pitted red cells) was used as an indicator of splenic function. Multicolor flow cytometry was performed to analyze circulating B cells.

RESULTS: A substantial clinical improvement in 10 of the 15 CD patients was associated with a significant reduction of pitted red cells (from median 6.0% to 3.6%; P < 0.01) after 10 weeks of treatment. In responder patients the improvement of splenic function was accompanied by a parallel increase of circulating IgM-memory B cells (from median 6.9% to 13.3%; P < 0.005). Splenic function was not ameliorated in nonresponder patients.

CONCLUSIONS: Splenic function improved in CD patients who responded to infliximab and was accompanied by a concomitant restoration of the IgM-memory B cell pool responsible for the protection against encapsulated bacteria. Restoration of splenic function after infliximab treatment is intriguing and requires further investigation.

Original languageEnglish
Pages (from-to)591-596
Number of pages6
JournalInflammatory Bowel Diseases
Volume14
Issue number5
Early online date31 Jan 2008
DOIs
Publication statusPublished - May 2008

Keywords

  • Adult
  • Anti-Inflammatory Agents/administration & dosage
  • Antibodies, Monoclonal/administration & dosage
  • B-Lymphocytes/immunology
  • Crohn Disease/blood
  • Dose-Response Relationship, Drug
  • Female
  • Flow Cytometry
  • Follow-Up Studies
  • Humans
  • Immunoglobulin M/immunology
  • Infliximab
  • Male
  • Microscopy, Interference
  • Middle Aged
  • Spleen/physiology
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha/antagonists & inhibitors

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